Significance Positron Emission Tomography (PET) is a unique tool to study the metabolism and function of the human brain. In this research project we have been able to utilize Magnetic Resonance Imaging (MRI) and PET to study metabolic changes in the brain of aged macaques. The aged rhesus macaques allows a unique opportunity to correlate anatomical and behavioral studies with metabolic data obtained from PET studies. Objectives The objectives of this study were to evaluate the relationship between regional cerebral metabolic rates for glucose and performance of a delayed response (DR) test of memory in the aged monkey. Metabolic rates for glucose were determined with the tracer (18F)fluorodeoxyglucose and imaging analysis was used to determine the regional cerebral metabolic rates for the injected glucose label (rCMRglc). We also begin preliminary studies to develop a metabolic tracer specific for the cholinergic systems in aged rhesus macaques. Results Eleven aged animals 21-26 years old were included in the final analysis. The aged animals exhibited significant DR deficits relative to a cohort of normal young monkeys. Variability in DR performance among the aged subjects was significantly correlated with relative hippocampal rCMRglc and chrononlogical age was a reliable predictor of orbitofrontal rCMRglc ratios. These results indicate a relationship in impaired DR performance in aged macaques and altered metabolism in multiple limbic strucutures involved in learinng and memory. Initial studies with a vesamicol label for cholinergic activity have shown nonspecific labeling that at present does not allow analysis of specific cholinergic function. Future Directions To further evaluate changes in specific neurotransmitters systems associated with aging future studies will focus on analysis of aged animals with both dopaminergic and cholinergic label systems. KEYWORDS PET, aging, hippocampus, memory